Phosphorus is present in a living body in various forms as constitutional elements important for the body, such as DNA, RNA or bone, and plays an important role in life-sustaining activities.
Phosphoric acid is mainly absorbed from food through the digestive tract in the form of inorganic phosphorus, and it is then eliminated through the kidney in the form of urine (Non Patent Literature 1).
Absorption of phosphorus through the digestive tract, elimination thereof through the kidney, and absorption and/or metabolism thereof from the bone are controlled by the action of vitamin D, parathyroid hormone (PTH), etc., and thus, the blood level of phosphorus is maintained constant.
In the case of renal failure, hyperphosphatemia in which the blood level of phosphorus shows an extremely high value is developed in many cases due to a reduction in elimination of phosphoric acid from the kidney. An excessive amount of phosphoric acid binds to blood calcium, and it causes ectopic calcification in the cardiovascular system, so that it seems to become a risk factor for cardiovascular diseases such as myocardial infarction (Non Patent Literature 2).
Moreover, hyperphosphatemia secondarily causes hypocalcemia, and in compensation, hyperparathyroidism characterized by an increase in the blood PTH level is developed. This also becomes a main factor for developing renal osteodystrophy. As mentioned above, hyperphosphatemia in chronic renal failure patients reduces the QOL of the patients due to bone fracture, bone pain, etc., and at the same time, it becomes a main factor for the death of chronic renal failure patients.
At present, as a therapeutic drug for hyperphosphatemia, there is used a phosphate adsorbent that adsorbs phosphoric acid in the digestive tract and thereby suppresses the absorption thereof, as well as diet restriction. As oral adsorbents, various medicaments such as calcium preparations (precipitated calcium carbonate, etc.), polymer preparations (sevelamer hydrochloride), and metallic salt preparations (aluminum hydroxide and lanthanum carbonate) have been used. It is pointed out that individual preparations have problems.
Regarding the calcium preparations, it has been demonstrated that vascular calcification is promoted due to hypercalcemia (Non Patent Literature 3), and the polymer preparations are problematic in terms of drug compliance caused by administration at a dose of several grams per day and digestive symptoms such as constipation and/or diarrhea (Non Patent Literature 4).
Moreover, regarding the metallic salt preparations, the risk of being accumulated in the body is pointed out (Non Patent Literature 5). Thus, sufficient therapeutic drugs for hyperphosphatemia have not yet been developed.
It has been reported that a sodium-dependent phosphate transporter expressed in small intestinal epithelial cells plays an important role in absorption of inorganic phosphate through the digestive tract (Non Patent Literature 6). It is anticipated that a compound that specifically inhibits the active transport of phosphate can suppress absorption of phosphorus through the digestive tract, more efficiently than oral adsorbents, and that it can improve the drug compliance that has been the problem of oral adsorbents and can solve the problems such as digestive symptoms and accumulation.
Under the aforementioned circumstances, it has been desired to develop a novel preparation for preventing or treating hyperphosphatemia or disease associated with hyperphosphatemia.
The compound described in WO2011/136269 is relevant to the compound of the present invention. However, this compound differs from the compound of the present invention in terms of essential partial structure.